Archive for the ‘Gene Therapy Research’ Category

Pfizer has chosen a site in Sanford, North Carolina for a gene therapy production plant, just 40 miles from its recent acquisition Bamboo Therapeutics Inc.

The US drug firm had been search for a site since March.

According to North Carolina Governor Roy Cooper, Pfizer will spend $100m (85m) on the new facility and has also committed $4m to support postdoctoral fellowships in North Carolina universities for training in gene therapy research.

The project will create jobs that deliver a total payroll impact of more than $3.9m each year to the community according to the North Carolina Department of Commerce and the Economic Development Partnership.

The project will be part funded by a $250,000 grant previously awarded to Wyeth which was acquired by Pfizer in 2009 - by the One North Carolina Fund, which helps local Governments attract economic investment.

Bamboo buy

The decision follows a little over a year after the US drug manufacturer acquired Bamboo Therapeutics, a North Carolina-based gene therapy developer.

The deal included a recombinant Adeno-Associated Virus (rAAV) vector design and production technology, a Phase I candidate for Giant Axonal Neuropathy and a preclinical programme targeting Duchenne Muscular Dystrophy (DMD).

Pfizer also gained a 11,000sq ft gene therapy manufacturing facility in Chapel Hill that Bamboo bought from the University of North Carolina in 2016.

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Pfizer chooses Sanford, North Carolina site for $100m gene therapy plant - BioPharma-Reporter.com

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Pfizer investing $100M in Sanford plant expansion, adding jobs ... Triangle Business Journal Pfizer has confirmed plans to invest $100 million in the expansion of its Sanford research and manufacturing plant. and more »

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Pfizer investing $100M in Sanford plant expansion, adding jobs ... - Triangle Business Journal

Regenxbio has joined forces with investment firm OrbiMed and a new nonprofit foundation to create Prevail Therapeutics, a startup focused on new biologics and gene therapiesfor Parkinson's disease (PD).

Prevail will draw on the expertise of the Silverstein Foundation for Parkinson's with GBA, which concentrates on a particular form of the disease caused by mutations in the glucocerebrosidase gene.

The foundation was set up this year by OrbiMed's co-head of private equity Jonathan Silverstein, who was diagnosed with GBA-linked PD in February and is mobilizing efforts to discover a cure for the disease. Silverstein backed the foundation with $10 million of his own money, and is intent on accelerating research into PD with GBA as well as other forms of the disease.

Prevail says it will focus initially on research coming out of the lab of its co-founder and CEO Asa Abeliovich, M.D., Ph.D., who is on the faculty of Columbia University as well as being a scientific adviser to the Silverstein Foundation and co-founder of neurodegenerative disease biotech Alector.

By joining forces with Regenxbio, Prevail launches with an exclusive license to the gene therapy specialist's adeno-associated virus (AAV) based vector technology NAV AAV9 for PD and other neurodegenerative disorders.

Silverstein said that the NAV platform and Dr. Abeliovich's "deep expertise in the molecular mechanisms of neurodegeneration provides us with a promising opportunity to develop potential life-changing therapies for patients suffering from Parkinson's disease and other neurodegenerative diseases."

He told CNBC today that Prevail's board will also have some big names, including Leonard Bell, co-founder and former CEO of Alexion, OrbiMed venture partner and Alexion co-founder Steve Squinto and serial entrepreneur Peter Thompson of Silverback Therapeutics and Corvus Pharmaceuticals.

The new company will initially focus on GBA1, the most common of the PD mutations, which is estimated to be present in up to 10% of U.S. PD patients and perhaps 100,000 people worldwide. The disease mechanism linked to the mutationan accumulation of alpha-synuclein in the brainmay have implications for the broader PD population and other neurodegenerative diseases.

"Many of the drugs we are trying for Parkinson's with GBA may work in the broader Parkinson's population," said Silverstein. The aim will be to get drugs approved for use in GBA patients first, and then expand their use into other patient groups.

The work of the foundation is attracting investment from companies who are not even active in PD, with cancer specialist Celgene today pledging a grant of $5 million.

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Silverstein-backed startup will test gene therapy for Parkinson's - FierceBiotech

Updated Aug. 8, 2017 at 7:02 a.m.

Published: 2017-08-07 16:07:00 Updated: 2017-08-08 07:02:05

Sanford, N.C. Pharmaceutical giant Pfizer Inc. plans to invest $100 million in its Sanford operations as part of a push into gene therapy, officials said Monday.

The effort builds on a technology developed at the University of North Carolina at Chapel Hill and will create 40 jobs in Sanford.

"Pfizer is proud to further expand our presence in North Carolina, particularly as we build our leadership in gene therapy," Lynn Bottone, site leader at Pfizer Sanford, said in a statement. "We look forward to the next phase of this expansion as we build a clinical and commercial manufacturing facility."

Preliminary work on the expansion and initial hiring have already begun. The 230-acre campus employs about 450 people, reports the N.C. Biotechnology Center.

Gene therapy is a potentially transformational technology for patients that involves highly specialized, one-time treatments to address the root cause of diseases caused by genetic mutation. The technology involves introducing genetic material into the body to deliver a correct copy of a gene to a patients cells to compensate for a defective or missing gene.

Last year, Pfizer acquired Bamboo Therapeutics Inc., a privately held biotechnology company in Chapel Hill focused on developing gene therapies for the potential treatment of patients with certain rare diseases related to neuromuscular conditions and those affecting the central nervous system. Pfizer also committed $4 million to support postdoctoral fellowships in North Carolina universities for training in gene therapy research.

"We are excited that Carolinas research will improve lives and create jobs for North Carolinians," UNC-Chapel Hill Chancellor Carol Folt said in a statement. "This is a perfect example of how placing innovation at the center of our university creates new opportunities. We are proud to be a part of the technologies, expertise and infrastructure that went into Bamboo Therapeutics and helped make this manufacturing expansion in Sanford possible. Gene therapy is a strength at Carolina, and we look forward to continue to help advance this industry."

Pfizer is also expanding a drug-manufacturing facility in Rocky Mount that it acquired from Hospira in 2015. The $190 million project will add 65,000 square feet of sterile injectable facilities but will not create any new jobs. The plant employs about 300 people.

Gov. Roy Cooper visited Pfizers Sanford facility last week to take a tour and meet with the companys senior leaders.

"North Carolina is one of the few places in the country with the biotech resources to take an idea all the way from the lab to the manufacturing line," Cooper said in a statement. "Pfizers investment in Lee County is a prime example of how North Carolinas world-class universities and cutting-edge industries work together to move our state forward."

Pfizer qualified for a performance-based grant of $250,000 from the One North Carolina Fund, which provides state assistance matched by local governments to help attract economic investment and create jobs. Companies receive no money upfront and must meet job and investment targets to obtain payment.

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Pfizer to invest $100M in Sanford gene therapy operation, add jobs ... - WRAL Tech Wire

Related ResearchPfizer Inc., one of the worlds premier biopharmaceutical companies, will expand its research-production facilities in Sanford, North Carolina. The company will prepare to produce new gene therapy medicines.

Governor Roy Cooper announced the company plans to invest $100 million in its research facility in Lee County, creating 40 jobs and building upon a technology first developed at the University of North Carolina at Chapel Hill.

The Pfizer expansion in Sanford will focus on gene therapy, a potentially transformational technology for patients, focused on highly specialized, one-time treatments that address the root cause of diseases caused by genetic mutation. The technology involves introducing genetic material into the body to deliver a correct copy of a gene to a patients cells to compensate for a defective or missing gene.

Pfizer is proud to further expand our presence in North Carolina, particularly as we build our leadership in gene therapy, states Lynn Bottone, Site Leader at Pfizer Sanford. We look forward to the next phase of this expansion as we build a clinical and commercial manufacturing facility.

As an incentive a performance-based grant of $250,000 from the One North Carolina Fund will help facilitate Pfizers expansion in Lee County. The One NC grant will formally be awarded to Wyeth Holdings, LLC, a wholly-owned subsidiary of Pfizer Inc.

The One NC Fund provides financial assistance to local governments to help attract economic investment and to create jobs. Companies receive no money upfront and must meet job creation and capital investment targets to qualify for payment. All One NC grants require a matching grant from local governments and any award is contingent upon that condition being met.

North Carolina is one of the few places in the country with the biotech resources to take an idea all the way from the lab to the manufacturing line, Governor Cooper said. Pfizers investment in Lee County is a prime example of how North Carolinas world-class universities and cutting-edge industries work together to move our state forward.

In 2016, the company acquired Bamboo Therapeutics, Inc., a privately held biotechnology company based in Chapel Hill focused on developing gene therapies for the potential treatment of patients with certain rare diseases related to neuromuscular conditions and those affecting the central nervous system. Pfizer also committed $4 million to support postdoctoral fellowships in North Carolina universities for training in gene therapy research.

Innovation drives economic opportunity and expansion, said North Carolina Commerce Secretary Anthony M. Copeland. Pfizers decision to expand in North Carolina proves how our investments in education pay off in new jobs and new solutions to the worlds toughest challenges.

We are excited that Carolinas research will improve lives and create jobs for North Carolinians, said Carol Folt, Chancellor of the University of North Carolina at Chapel Hill. This is a perfect example of how placing innovation at the center of our university creates new opportunities. We are proud to be a part of the technologies, expertise and infrastructure that went into Bamboo Therapeutics and helped make this manufacturing expansion in Sanford possible. Gene therapy is a strength at Carolina and we look forward to continue to help advance this industry.

The North Carolina Department of Commerce and the Economic Development Partnership of N.C. (EDPNC) were instrumental in supporting the companys investment decision. In addition to North Carolina Commerce and the Economic Partnership of North Carolina, other key partners in the project include the North Carolina General Assembly, the North Carolina Community College System, the University of North Carolina at Chapel Hill, the North Carolina Biotechnology Center, Duke Energy, Lee County, and the Sanford Area Growth Alliance.

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Pfizer Inc. Expands Biopharmaceutical Research Center in Sanford, North Carolina - Area Development Online

By Ben Hirschler

LONDON (Reuters) - The science of gene therapy is finally delivering on its potential, and drugmakers are now hoping to produce commercially viable medicines after tiny sales for the first two such treatments in Europe.

Thanks to advances in delivering genes to targeted cells, more treatments based on fixing faulty DNA in patients are coming soon, including the first ones in the United States.

Yet the lack of sales for the two drugs already launched to treat ultra-rare diseases in Europe highlights the hurdles ahead for drugmakers in marketing new, extremely expensive products for genetic diseases.

After decades of frustrations, firms believe there are now major opportunities for gene therapy in treating inherited conditions such as haemophilia. They argue that therapies offering one-off cures for intractable diseases will save health providers large sums in the long term over conventional treatments which each patient may need for years.

In the past five years, European regulators have approved two gene therapies - the first of their kind in the world, outside China - but only three patients have so far been treated commercially.

UniQure's Glybera, for a very rare blood disorder, is now being taken off the market given lack of demand.

The future of GlaxoSmithKline's Strimvelis for ADA-SCID - or "bubble boy" disease, where sufferers are highly vulnerable to infections - is uncertain after the company decided to review and possibly sell its rare diseases unit.

Glybera, costing around $1 million per patient, has been used just once since approval in 2012. Strimvelis, at about $700,000, has seen two sales since its approval in May 2016, with two more patients due to be treated later this year.

"It's disappointing that so few patients have received gene therapy in Europe," said KPMG chief medical adviser Hilary Thomas. "It shows the business challenges and the problems faced by publicly-funded healthcare systems in dealing with a very expensive one-off treatment."

These first two therapies are for exceptionally rare conditions - GSK estimates there are only 15 new cases of ADA-SCID in Europe each year - but both drugs are expected to pave the way for bigger products.

The idea of using engineered viruses to deliver healthy genes has fuelled experiments since the 1990s. Progress was derailed by a patient death and cancer cases, but now scientists have learnt how to make viral delivery safer and more efficient.

Spark Therapeutics hopes to win U.S. approval in January 2018 for a gene therapy to cure a rare inherited form of blindness, while Novartis could get a U.S. go-ahead as early as next month for its gene-modified cell therapy against leukaemia - a variation on standard gene therapy.

At the same time, academic research is advancing by leaps and bounds, with last week's successful use of CRISPR-Cas9 gene editing to correct a defect in a human embryo pointing to more innovative therapies down the line.

Spark Chief Executive Jeffrey Marrazzo thinks there are specific reasons why Europe's first gene therapies have sold poorly, reflecting complex reimbursement systems, Glybera's patchy clinical trials record and the fact Strimvelis is given at only one clinic in Italy.

He expects Spark will do better. It plans to have treatment centers in each country to address a type of blindness affecting about 6,000 people around the world.

Marrazzo admits, however, there are many questions about how his firm should be rewarded for the $400 million it has spent developing the drug, given that healthcare systems are geared to paying for drugs monthly rather than facing a huge upfront bill.

A one-time cure, even at $1 million, could still save money over the long term by reducing the need for expensive care, in much the same way that a kidney transplant can save hundreds of thousands of dollars in dialysis costs.

But gene therapy companies - which also include Bluebird Bio, BioMarin, Sangamo and GenSight - may need new business models.

One option would be a pay-for-performance system, where governments or insurers would make payments to companies that could be halted if the drug stopped working.

"In an area like haemophilia I think that approach is going to make a ton of sense, since the budget impact there starts to get more significant," Marrazzo said.

Haemophilia, a hereditary condition affecting more than 100,000 people in markets where specialty drugmakers typically operate, promises to be the first really big commercial opportunity. It offers to free patients from regular infusions of blood-clotting factors that can cost up to $400,000 a year.

Significantly, despite its move away from ultra-rare diseases, GSK is still looking to use its gene therapy platform to develop treatments for more common diseases, including cancer and beta-thalassaemia, another inherited blood disorder.

Rivals such as Pfizer and Sanofi are also investing, and overall financing for gene and gene-modified cell therapies reached $1 billion in the first quarter of 2017, according to the Alliance of Regenerative Medicine.

Shire CEO Flemming Ornskov - who has a large conventional haemophilia business and is also chasing Biomarin and Spark in hunting a cure for the bleeding disorder - sees both the opportunities and the difficulties of gene therapy.

"Is it something that I think will take market share mid- to long-term if the data continues to be encouraging? Yes. But I think everybody will have to figure out a business model."

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Gene Therapy Is Now Available, but Who Will Pay for It? - Scientific American

CAMBRIDGE, Mass. & TOKYO--(BUSINESS WIRE)--Agilis Biotherapeutics, Inc. (Agilis), a biotechnology company advancing innovative DNA therapeutics for rare genetic diseases that affect the central nervous system (CNS), and Gene Therapy Research Institution Co, Ltd. (GTRI), a corporation with the mission of developing and delivering of the safest and most efficient gene therapies, today announced that the companies have completed a manufacturing and collaboration partnership joint venture (JV) to advance adeno-associated virus (AAV) gene therapies. The JV was initiated earlier this year in connection with a grant from the Japanese Ministry of Trade, Economics and Industry (METI) and Japan External Trade Organization (JETRO) for the development of a state-of-the-art AAV manufacturing facility in Japan. GTRI was co-founded by Professor Shin-ichi Muramatsu, M.D., a leading pioneer in gene therapy who has performed basic science and clinical research in the field for over two decades.

The JV, headquartered in Japan, will initially focus on developing and manufacturing AAV gene therapy vectors using Sf9 baculovirus and HEK293 mammalian cell systems and operate a process development and production facility located in the Tokyo area designed to meet international manufacturing standards, including cGMP, GCTP and PIC/S GMP requirements. Agilis and GTRI will also collaborate to expedite the development, approval and commercialization of select gene therapies in specific CNS diseases. Terms of the joint venture were not disclosed.

We are pleased to collaborate with Agilis to leverage each organizations capabilities and know-how, advance the manufacturing state-of-the art for gene therapy, and develop novel gene therapies, commented Katsuhito Asai, Chief Executive Officer of GTRI and a Director of the joint venture. Our partnership will seek to capitalize on the strong recent progress in the field of gene therapy and expedite the development of innovative gene therapies for patients in need, with a major emphasis on the quality production of safe, effective therapeutics.

We are thrilled to partner with GTRI, said Mark Pykett, Agilis CEO and a Director of the joint venture. We believe that our partnership will enhance the efforts of both organizations, build important shared production capabilities, and accelerate development and commercialization of important gene therapies. We look forward to working with GTRI on a range of initiatives.

Agilis Biotherapeutics

Agilis is advancing innovative gene therapies designed to provide long-term efficacy for patients with debilitating, often fatal, rare genetic diseases that affect the central nervous system. Agilis gene therapies are engineered to impart sustainable clinical benefits by inducing persistent expression of a therapeutic gene through precise targeting and restoration of lost gene function to achieve long-term efficacy. Agilis rare disease programs are focused on gene therapy for AADC deficiency, Friedreichs ataxia, and Angelman syndrome, all rare genetic diseases that include neurological deficits and result in physically debilitating conditions.

We invite you to visit our website at http://www.agilisbio.com

About GTRI

GTRI, a bio-tech venture in Japan, was founded in May 2014 based on the pioneering research of Dr. Shin-ichi Muramatsu, focusing on gene therapy using AAV vector as the leading company in Japan in this field. Its pipeline includes more than 20 diseases, targeting CNS diseases and monogenic disorders, such as Parkinsons disease, AADC deficiency, ALS, Alzheimers disease, spinocerebellar degeneration, Tay-Sachs disease, GLUT1 deficiency, and others.

Dr. Muramatsu, PhD, MD, of Jichi Medical University, is one of the top researchers of AAV vectors and AAV-mediated gene therapy in the world. He originated AAV3 in 1995 during his research at the NIH, USA, and afterwards developed his original modified AAV3/9 in Japan, which enables to deliver the gene of interest effectively in CNS through the blood-brain barrier.

Safe Harbor Statement

Some of the statements made in this press release are forward-looking statements. These forward-looking statements are based upon our current expectations and projections about future events and generally relate to our plans, objectives and expectations for the development of our business. Although management believes that the plans and objectives reflected in or suggested by these forward-looking statements are reasonable, all forward-looking statements involve risks and uncertainties and actual future results may be materially different from the plans, objectives and expectations expressed in this press release.

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Agilis Biotherapeutics and Gene Therapy Research Institution Enter ... - Business Wire (press release)

Coronary heart disease is the term that describes what happens when the heart's blood supply is blocked or interrupted by a build-up of fatty substances in the coronary arteries.

This is a process called atherosclerosis.

Coronary heart disease can't be cured yet but treatment can help manage the symptoms and reduce the chances of problems such as heart attacks.

However, now experts have found a new gene therapy which targets the heart and requires only one treatment session.

The treatment has been found safe for patients with coronary artery disease, according to a successful trial carried out in Finland.

It works by enhancing circulation in the oxygen-deficient heart muscle and experts said the effects were visible even one year after the treatment.

A trial was carried out in collaboration between the University of Eastern Finland, Kuopio University Hospital and Turku PET Centre as part of the Centre of Excellence in Cardiovascular and Metabolic Diseases of the Academy of Finland.

The biological bypass is based on gene transfer in which a natural human growth hormones - called a factor - is injected into the heart muscle to enhance vascular growth.

The trial was the first in the world to use a vascular growth factor which has several beneficial effects on circulation in the heart muscle.

Experts also developed a precise method for injecting the gene into the oxygen-deficient heart muscle area.

A customised catheter is inserted via the patients groin vessels to the left ventricle, after which the gene solution can be injected directly into the heart muscle.

The method is as easy to perform as coronary balloon angioplasty, which means that it is also suitable for older patients and patients who are beyond a bypass surgery or other demanding surgical or arterial operations.

Experts said the biological bypass constitutes a significant step forward in the development of novel biological treatments for patients with severe coronary artery disease.

A new blood test biomarker was also discovered, making it possible to identify patients who are most likely to benefit from the new treatment.

The biological bypass was developed by a research group at the University of Eastern Finland.

Experts said research into the biological bypass will continue with a new trial set to start in 2018.

This trial will also include five other cardiology clinics from Denmark, the UK, Austria, Spain and Poland.

This comes after it was revealed heart disease risk could be determined by your waist size.

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Cardiovascular disease cure? One session of THIS could help treat condition - Express.co.uk

Using a powerful gene-editing technique, scientists have rid human embryos of a mutation that causes an inherited form of heart disease often deadly to healthy young athletes and adults in their prime.

The experiment marks the first time that scientists have altered the human genome to ensure a disease-causing mutation would disappear not only from the DNA of the subject on which its performed, but from the genes of his or her progeny as well.

The controversial procedure, known as germ-line editing, was conducted at Oregon Health & Science University using human embryos expressly created for the purpose. It was reported in the journal Nature.

The new research comes less than six months after the National Academies of Science, Engineering and Medicine recommended that scientists limit their trials of human germ-line editing to diseases that could not be treated with reasonable alternatives at least for now.

In a bid to make the experiment relevant to real-life dilemmas faced by parents who carry genes for inherited diseases, the researchers focused their editing efforts on a mutation that causes inherited hypertrophic cardiomyopathy.

In this genetic condition, a parent who carries one normal and one faulty copy of a the MYBPC3 gene has a 50-50 chance of passing that mutation on to his or her offspring. If the child inherits the mutation, his or her heart muscle is likely to grow prematurely weak and stiff, causing heart failure and often early death.

In diseases where one parent carries such an autosomal dominant mutation, a couple will often seek the assistance of fertility doctors to minimise the risk of passing such a mutation on to a child. A womans egg production is medically stimulated, and eggs and sperm meet in a lab a process called in vitro fertilisation. Then embryologists inspect the resulting embryos, cull the ones that have inherited an unwanted mutation, and transfer only unaffected embryos into a womans uterus to be carried to term.

In the new research, researchers set out to test whether germ-line gene editing could make the process of choosing healthy embryos more effective and efficient by creating more of them.

In the end, their experiment showed it could. The targeted correction of a disease-causing gene carried by a single parent can potentially rescue a substantial portion of mutant human embryos, thus increasing the number of embryos available for transfer, the authors wrote in Nature. Co-author Dr Paula Amato, an Oregon Health & Science University (OHSU) professor of obstetrics and gynaecology, said the technique could potentially decrease the number of cycles needed for people trying to have children free of genetic disease if its found safe for use in fertility clinics.

Along the way, though, many of the researchers findings were scientifically surprising. Long-feared effects of germ-line editing, including collateral damage to off-target genetic sequences, scarcely materialised. And mosaicism, a phenomenon in which edited DNA appears in some but not all cells, was found to be minimal.

The studys lead author, OHSU biologist Shoukhrat Mitalipov, called these exciting and surprising moments. But he cautioned that there is room to improve the techniques demonstrated to produce mutation-free embryos. As for conducting human clinical trials of the germ-line correction, he said those would have to wait until results showed a near-perfect level of efficiency and accuracy, and could be limited by state and federal regulations.

Eventually, Mitalipov said, such germ-line gene editing might also make it easier for parents who carry other gene mutations that follow a similar pattern of inheritance including some that cause breast and ovarian cancers, cystic fibrosis and muscular dystrophy to have healthy children who would not pass those genes to their own offspring.

There is still a long road ahead, predicted Mitalipov, who heads the Centre for Embryonic Cell and Gene Therapy at the Portland university.

The research drew a mix of praise and concern from experts in genetic medicine.

Dr Richard O. Hynes, who co-chaired the National Academies report issued in February, called the new study very good science that advances understanding of genetic repair on many fronts. Hynes, who was not involved with the latest research effort, said he was pleasantly surprised by researchers clever modifications and their outcomes.

Its likely to become feasible, technically not tomorrow, not next year, but in some foreseeable time. Less than a decade, Id say, said Haynes, a biologist and cancer researcher at MIT and the Howard Hughes Medical Institute.

University of California, Berkeley molecular and cell biologist Jennifer Doudna, one of pioneers of the CRISPR-Cas9 gene-editing technique, acknowledged the new research highlights a prospective use of gene editing for one inherited disease and offers some insights into the process.

But Doudna questioned how broadly the experiments promising results would apply to other inherited diseases. She said she does not believe the use of germ-line editing as a means to improve efficiency at infertility clinics meets the criteria laid out by the National Academies of Science, which urged that the techniques only be explored as treatment for diseases with no reasonable alternative.

Already, 50 per cent of embryos would be normal, said Doudna. Why not just implant those?

Doudna said she worried that the new findings will encourage people to proceed down this road before the scientific and ethical implications of germ-line editing have been fully considered.

A large group of experts concluded that clinical use should not proceed until and unless theres broad societal consensus, and that just hasnt happened, Doudna said. This study underscores the urgency of having those debates. Because its coming.

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Human embryos 'edited' from potentially fatal gene mutation - Jordan Times

Agilis Biotherapeutics, Inc. (Agilis), a biotechnology company advancing innovative DNA therapeutics for rare genetic diseases that affect the central nervous system (CNS), and Gene Therapy Research Institution Co, Ltd. (GTRI), a corporation with the mission of developing and delivering of the safest and most efficient gene therapies, announced that the companies have completed a manufacturing and collaboration partnership joint venture (JV) to advance adeno-associated virus (AAV) gene therapies. The JV was initiated earlier this year in connection with a grant from the Japanese Ministry of Trade, Economics and Industry (METI) and Japan External Trade Organization (JETRO) for the development of a state-of-the-art AAV manufacturing facility in Japan. GTRI was co-founded by Professor Shin-ichi Muramatsu, M.D., a leading pioneer in gene therapy who has performed basic science and clinical research in the field for over two decades.

The JV, headquartered in Japan, will initially focus on developing and manufacturing AAV gene therapy vectors using Sf9 baculovirus and HEK293 mammalian cell systems and operate a process development and production facility located in the Tokyo area designed to meet international manufacturing standards, including cGMP, GCTP and PIC/S GMP requirements. Agilis and GTRI will also collaborate to expedite the development, approval and commercialization of select gene therapies in specific CNS diseases. Terms of the joint venture were not disclosed.

We are pleased to collaborate with Agilis to leverage each organizations capabilities and know-how, advance the manufacturing state-of-the art for gene therapy, and develop novel gene therapies, commented Katsuhito Asai, Chief Executive Officer of GTRI and a Director of the joint venture. Our partnership will seek to capitalize on the strong recent progress in the field of gene therapy and expedite the development of innovative gene therapies for patients in need, with a major emphasis on the quality production of safe, effective therapeutics.

We are thrilled to partner with GTRI, said Mark Pykett, Agilis CEO and a Director of the joint venture. We believe that our partnership will enhance the efforts of both organizations, build important shared production capabilities, and accelerate development and commercialization of important gene therapies. We look forward to working with GTRI on a range of initiatives.

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Agilis Biotherapeutics, Gene Therapy Research Institution Enter Strategic Partnership - Drug Discovery & Development

In BriefThis is truly the golden age of anti-aging research, with extended telemores, senescent cell therapies, and young-blood transfusions being three of the most promising treatment avenues. However, even if one of these therapies proves to be the proverbial "fountain of youth," the financial cost of a long, healthy life is still well out of reach for most people.

The idea of never growing old is seductive, but it has remained a pipe-dream throughout history. However, that may not be the case for much longer as the scientific community has seen a surge in anti-aging research in recent years.All across the globe, researchers are now exploring different methods to combat aging and extend human health span (the number of years of good health a person experiences).

The avenue that is arguably generating the most support involves telemores. These are the caps that sit on the ends of chromosomes. They provide protection for the DNA molecules, and their length has been linked to good health. Unfortunately, they shrinkwith every division until they can no longer protect the cell and it dies or damages surrounding cells through senescence.

So far, the research on telemores has been promising.Maria Blasco of the Spanish National Cancer Research Centre used gene therapy to extendthe telemores in mice, which led to a 40 percent increase in lifespan.

Meanwhile Helen Blau, Director of the Baxter Laboratory for Stem Cell Biology at Stanford, modified the RNA of skin cells to increase telemore length. This caused the cells to divide up to 40 moretimes than their untreated counterparts did before dying or stagnating.

Another promising avenue of anti-aging research involved targeting senescent cells. These cells pump out chemicals as they deteriorate that are damaging to their neighboring cells, causing many of the diseases associated with aging, so researchers have been looking for ways to either inhibit their development or periodically purge them.

At the Mayo Clinic in Rochester, Minnesota,Darren Bakerand his colleagues found that giving mice a drug that destroyed these cells delayed the development of the diseases of aging, as well as made the mice look plumper and younger.

At the slightly more unsettlingend of the anti-aging treatment spectrum is the process of transfusing the blood of the young into the old. Despite the vampiric and macabre nature of the treatment, researchers have found evidence that it is effective. Individuals who receive blood from younger donors report health benefits, such as lowered cholesterol levels, while older mice have been shown to be rejuvenated by injections of blood from younger mice or evenhuman teenagers.

While science is movingquickly toward a future in which aging and its consequences are obsolete, the few commercial means of receiving the treatments above are, at present, extremely expensive.

Liz Parrishis not a biologist by training, but she did enlist the help of scientists to develop the telemore-based treatment offered by her company,BioViva. Ostensibly, Parrish has developed an injection based on Blancos principles, andshe herself is patient zero, having already injected herself with that telomere-extending treatment as well as one designed to preserve muscle mass. While BioVivahasnt gone to market yet, Parrish told New Humanist that eachinjection costs between $200,000 to $400,000 to produce.

While no commercial means of senescent cell therapy exists as of yet, individuals can buy young blood transfusions. Jesse Karmazins company Ambrosia offers blood plasma transfusions for anyone willing to pay $8,000.

However, Stanford University neuroscientist Tony Wyss-Coray, who has conducted numerous experiments on mices reaction to young blood, thinks youd be better off saving your money. He dismisses the science behind the treatment,telling MIT Technology Review that people want to believe that young blood restores youth, even though we dont have evidence that it works in humans.

For the moment, anti-aging therapies are attainable in theory, but well out of financial reach for all except a wealthy few. Once the science is crystallized, however, the treatments should become exponentially cheaper, and a long, healthy life will be neither a pipe dream nor a hideously expensive commodity.

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Researchers Are Finding Remarkable Ways to Combat Aging and Extend Human Health - Futurism

An international team of researchers recently published, in the journal Nature, their study using genome editing to correct a heterozygous mutation in human preimplantation embryos using a technique called CRISPR-Cas9. This bench research, while far from bedside use, raises questions about the medical ethics of what could be considered genetic engineering. The AMA Code of Medical Ethics has guidance for physicians conducting research in this area.

In Opinion 7.3.6, Research in Gene Therapy and Genetic Engineering, the Code explains:

Gene therapy involves the replacement or modification of a genetic variant to restore or enhance cellular function or the improve response to nongenetic therapies. Genetic engineering involves the use of recombinant DNA techniques to introduce new characteristics or traits. In medicine, the goal of gene therapy and genetic engineering is to alleviate human suffering and disease. As with all therapies, this goal should be pursued only within the ethical traditions of the profession, which gives primacy to the welfare of the patient.

In general, genetic manipulation should be reserved for therapeutic purposes. Efforts to enhance desirable characteristics or to improve complex human traits are contrary to the ethical tradition of medicine. Because of the potential for abuse, genetic manipulation of nondisease traits or the eugenic development of offspring may never be justifiable.

Moreover, genetic manipulation can carry risks to both the individuals into whom modified genetic material is introduced and to future generations. Somatic cell gene therapy targets nongerm cells and thus does not carry risk to future generations. Germ-line therapy, in which a genetic modification is introduced into the genome of human gametes or their precursors, is intended to result in the expression of the modified gene in the recipients offspring and subsequent generations. Germ-line therapy thus may be associated with increased risk and the possibility of unpredictable and irreversible results that adversely affect the welfare of subsequent generations.

Thus, in addition to fundamental ethical requirements for the appropriate conduct of research with human participants, research in gene therapy or genetic engineering must put in place additional safeguards to vigorously protect the safety and well-being of participants and future generations.

Physicians should not engage in research involving gene therapy or genetic engineering with human participants unless the following conditions are met:

(a) Participate only in those studies for which they have relevant expertise.

(b) Ensure that voluntary consent has been obtained from each participant or from the participants legally authorized representative if the participant lacks the capacity to consent, in keeping with ethics guidance. This requires that:

(i) prospective participants receive the information they need to make well-considered decisions, including informing them about the nature of the research and potential harms involved;

(ii) physicians make all reasonable efforts to ensure that participants understand the research is not intended to benefit them individually;

(iii) physicians also make clear that the individual may refuse to participate or may withdraw from the protocol at any time.

(c) Assure themselves that the research protocol is scientifically sound and meets ethical guidelines for research with human participants. Informed consent can never be invoked to justify an unethical study design.

(d) Demonstrate the same care and concern for the well-being of research participants that they would for patients to whom they provide clinical care in a therapeutic relationship. Physician researchers should advocate for access to experimental interventions that have proven effectiveness for patients.

(e) Be mindful of conflicts of interest and assure themselves that appropriate safeguards are in place to protect the integrity of the research and the welfare of human participants.

(f) Adhere to rigorous scientific and ethical standards in conducting, supervising, and disseminating results of the research.

AMA Principles of Medical Ethics: I,II,III,V

At the 2016 AMA Interim Meeting, the AMA House of Delegates adopted policy on genome editing and its potential clinical use. In the policy, the AMA encourages continued research into the therapeutic use of genome editing and also urges continued development of consensus international principles, grounded in science and ethics, to determine permissible therapeutic applications of germline genome editing.

Chapter 7 of the Code, Opinions on Research & Innovation, also features guidance on other research-related subjects, including informed consent, conflicts of interest, use of placebo controls, and the use of DNA databanks.

The Code of Medical Ethics is updated periodically to address the changing conditions of medicine. The new edition, adopted in June 2016, is the culmination of an eight-year project to comprehensively review, update and reorganize guidance to ensure that the Code remains timely and easy to use for physicians in teaching and in practice.

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Genome editing and the AMA Code of Medical Ethics - American Medical Association (blog)

Alliance for Gene Cancer Therapy Executive Director Margaret C. Cianci and President and CEO John E. Walter outside the nonprofits headquarters in Stamford. Photo by Phil Hall.

The development of an experimental gene-targeting therapy in cancer treatment that could be approved for the U.S. market this year was sparked in large part by the research funding support of a Stamford nonprofit.

The chimeric antigen receptor T-cell (CAR-T) drug, labeled tisagenlecleucel by its manufacturer, Novartis, in July was unanimously recommended for approval by the oncologic drugs advisory committee of the U.S. Food and Drug Administration. If the FDA grants final approval as expected this fall, it will be the first drug treatment targeting human genes approved for the U.S. market.

In Stamford, the Alliance for Cancer Gene Therapy since 2004 has provided a total of $1.8 million to Dr. Carl June at the University of Pennsylvania, the lead researcher in developing the CAR-T therapy. John E. Walter, president and CEO of the Stamford organization, said Junes work has helped to redefine perceptions of what gene therapy can accomplish.

Oftentimes, gene therapy is perceived as taking the bad genes out and putting some good genes in, Walter said. In this case, a patients T-cells are being removed and re-engineered with a virus and reintroduced in the body. With this genetic re-engineering, they become killer T-cells they go in and go after and kill the cancer cells.

Cancer cells in your body multiply and dont know how to die, said Alliance for Gene Cancer Therapy Executive Director Margaret C. Cianci. We have cells in our system all of the time that are growing and dying, but cancer cells dont do that. This therapy is for supercharging your own immune system to recognize these cancer cells and kill them.

If approved, the Novartis drug would mark a milestone achievement for the Alliance, whose creation in 2001 was driven by a tragic loss caused by cancer in its co-founders family. Edward Netter, chairman and CEO of Geneve Corp., a financial services holding company in Stamford, and his wife Barbara, a staff therapist at Pelham Family Services in Westchester County, lost their daughter-in-law, Kimberly Lawrence-Netter, to breast cancer. Edward Netter died from cancer in 2011. His wife serves as the nonprofits honorary board chairwoman.

Walter, who served as CEO of the Leukemia & Lymphoma Society before joining the Alliance in May 2016, noted that this organization differed from most because all of its raised funds are used solely to finance research. Our administrative expenses are paid for by our board and by the Netters, he said, and the nonprofits four-person staff works out of Geneve Corp. headquarters. One hundred percent of your contributions go to research.

Since its founding, the Alliance has allocated approximately $29 million in grants to U.S. and Canadian projects. These are grants to two different types of scientists, said Cianci. We started funding young investigators at assistant professor level who have just become independent. It is difficult for them to get funding, especially in an area as innovative as gene therapy, and the government doesnt like to fund what they see as high-risk projects. We also fund clinical investigators, which included Dr. June.

The Alliance puts out two requests for funding applications each year, which are judged through a peer-review process coordinated by a scientific advisory committee.

There is always more research than there are dollars, said Walter. Invariably, we are leaving research on the table because we dont have the dollars to fund those.

The nonprofit itself receives funding through contributions from longtime donors and an annual fundraising event coordinated by Swim Across America that is held in the Long Island Sound directly across from its offices. That raises about $400,000 a year, Walter said.

Dr. Junes Alliance-funded research was published in a medical journal in 2011 in a study of three patients with advanced chronic lymphocytic leukemia. Novartis, the Swiss pharmaceutical company, expressed interest in the results and paid the University of Pennsylvania $20 million to license the technology.

Once we have survival data for these patients in Novartis-sponsored clinical trials, over time the FDA could consider using this as frontline treatment instead of highly toxic chemotherapy, said Walter.

For Cianci, the Alliances mission is crucial in encouraging new generations of researchers to focus on cancer and gene therapy solutions, especially when federal funding is being threatened by budget cuts.

If we dont fund the young scientists, they are going to leave the field, she warned. We dont want to lose some of these incredible minds. The average age for getting your first grant from the National Institute of Health is 42. What do you tell someone who just became a postdoctoral researcher and wants to have their own lab? How are they going to get funding?

One in four people could potentially get cancer in their lifetimes, Cianci said. And who hasnt been touched by cancer in one way or another?

Read more:
Gene therapy cancer treatment funded by Stamford nonprofit awaits FDA approval - Westfair Online

Weve always said in the past gene editing shouldnt be done, mostly because it couldnt be done safely, said Richard Hynes, a cancer researcher at the Massachusetts Institute of Technology who co-led the committee. Thats still true, but now it looks like its going to be done safely soon, he said, adding that the research is a big breakthrough.

What our report said was, once the technical hurdles are cleared, then there will be societal issues that have to be considered and discussions that are going to have to happen. Nows the time.

Scientists at Oregon Health and Science University, with colleagues in California, China and South Korea, reported that they repaired dozens of embryos, fixing a mutation that causes a common heart condition that can lead to sudden death later in life.

If embryos with the repaired mutation were allowed to develop into babies, they would not only be disease-free but also would not transmit the disease to descendants.

The researchers averted two important safety problems: They produced embryos in which all cells not just some were mutation-free, and they avoided creating unwanted extra mutations.

It feels a bit like a one small step for (hu)mans, one giant leap for (hu)mankind moment, Jennifer Doudna, a biochemist who helped discover the gene-editing method used, called CRISPR-Cas9, said in an email.

Scientists tried two techniques to remove a dangerous mutation. In the first, genetic scissors were inserted into fertilized eggs. The mutation was repaired in some of the resulting embryos but not always in every cell. The second method worked better: By injecting the scissors along with the sperm into the egg, more embryos emerged with repaired genes in every cell.

When gene-editing components were introduced into a fertilized egg, some embryos contained a patchwork of repaired and unrepaired cells.

Gene-editing

components inserted

after fertilization

Cell with

unrepaired

gene

Mosaicism in

later-stage embryo

When gene-editing components were introduced with sperm to the egg before fertilization, more embryos had repaired mutations in every cell.

Gene-editing components

inserted together with sperm,

before fertilization

In 42 of 58

embryos

tested, all

cells were

repaired

Uniform

later-stage embryo

When gene-editing components were introduced into a fertilized egg, some embryos contained a patchwork of repaired and unrepaired cells.

Gene-editing

components inserted

after fertilization

Cell with

unrepaired

gene

Mosaicism in

later-stage embryo

When gene-editing components were introduced with sperm to the egg before fertilization, more embryos had repaired mutations in every cell.

Gene-editing

components inserted

together with sperm,

before fertilization

In 42 of 58

embryos

tested, all

cells were

repaired

Uniform

later-stage embryo

I expect these results will be encouraging to those who hope to use human embryo editing for either research or eventual clinical purposes, said Dr. Doudna, who was not involved in the study.

Much more research is needed before the method could be tested in clinical trials, currently impermissible under federal law. But if the technique is found to work safely with this and other mutations, it might help some couples who could not otherwise have healthy children.

Potentially, it could apply to any of more than 10,000 conditions caused by specific inherited mutations. Researchers and experts said those might include breast and ovarian cancer linked to BRCA mutations, as well as diseases like Huntingtons, Tay-Sachs, beta thalassemia, and even sickle cell anemia, cystic fibrosis or some cases of early-onset Alzheimers.

You could certainly help families who have been blighted by a horrible genetic disease, said Robin Lovell-Badge, a professor of genetics and embryology at the Francis Crick Institute in London, who was not involved in the study.

You could quite imagine that in the future the demand would increase. Maybe it will still be small, but for those individuals it will be very important.

The researchers also discovered something unexpected: a previously unknown way that embryos repair themselves.

In other cells in the body, the editing process is carried out by genes that copy a DNA template introduced by scientists. In these embryos, the sperm cells mutant gene ignored that template and instead copied the healthy DNA sequence from the egg cell.

We were so surprised that we just couldnt get this template that we made to be used, said Shoukhrat Mitalipov, director of the Center for Embryonic Cell and Gene Therapy at Oregon Health and Science University and senior author of the study. It was very new and unusual.

The research significantly improves upon previous efforts. In three sets of experiments in China since 2015, researchers seldom managed to get the intended change into embryonic genes.

And some embryos had cells that did not get repaired a phenomenon called mosaicism that could result in the mutation being passed on as well as unplanned mutations that could cause other health problems.

In February, a National Academy of Sciences, Engineering and Medicine committee endorsed modifying embryos, but only to correct mutations that cause a serious disease or condition and when no reasonable alternatives exist.

Sheldon Krimsky, a bioethicist at Tufts University, said the main uncertainty about the new technique was whether reasonable alternatives to gene editing already exist.

As the authors themselves noted, many couples use pre-implantation genetic diagnosis to screen embryos at fertility clinics, allowing only healthy ones to be implanted. For these parents, gene editing could help by repairing mutant embryos so that more disease-free embryos would be available for implantation.

Hank Greely, director of the Center for Law and the Biosciences at Stanford, said creating fewer defective embryos also would reduce the number discarded by fertility clinics, which some people oppose.

The larger issue is so-called germline engineering, which refers to changes made to embryo that are inheritable.

If youre in one camp, its a horror to be avoided, and if youre in the other camp, its desirable, Dr. Greely said. Thats going to continue to be the fight, whether its a feature or a bug.

For now, the fight is theoretical. Congress has barred the Food and Drug Administration from considering clinical trials involving germline engineering. And the National Institutes of Health is prohibited from funding gene-editing research in human embryos. (The new study was funded by Oregon Health and Science University, the Institute for Basic Science in South Korea, and several foundations.)

The authors say they hope that once the method is optimized and studied with other mutations, officials in the United States or another country will allow regulated clinical trials.

I think it could be widely used, if its proven safe, said Dr. Paula Amato, a co-author of the study and reproductive endocrinologist at O.H.S.U. Besides creating more healthy embryos for in vitro fertilization, she said, it could be used when screening embryos is not an option or to reduce arduous IVF cycles for women.

Dr. Mitalipov has pushed the scientific envelope before, generating ethical controversy with a so-called three-parent baby procedure that would place the nucleus of the egg of a woman with defective cellular mitochondria into the egg from a healthy woman. The F.D.A. has not approved trials of the method, but Britain may begin one soon.

The new study involves hypertrophic cardiomyopathy, a disease affecting about one in 500 people, which can cause sudden heart failure, often in young athletes.

It is caused by a mutation in a gene called MYBPC3. If one parent has a mutated copy, there is a 50 percent chance of passing the disease to children.

Using sperm from a man with hypertrophic cardiomyopathy and eggs from 12 healthy women, the researchers created fertilized eggs. Injecting CRISPR-Cas9, which works as a genetic scissors, they snipped out the mutated DNA sequence on the male MYBPC3 gene.

They injected a synthetic healthy DNA sequence into the fertilized egg, expecting that the male genome would copy that sequence into the cut portion. That is how this gene-editing process works in other cells in the body, and in mouse embryos, Dr. Mitalipov said.

Instead, the male gene copied the healthy sequence from the female gene. The authors dont know why it happened.

Maybe human sex cells or gametes evolved to repair themselves because they are the only cells that transmit genes to offspring and need special protection, said Juan Carlos Izpisua Belmonte, a co-author and geneticist at the Salk Institute.

Out of 54 embryos, 36 emerged mutation-free, a significant improvement over natural circumstances in which about half would not have the mutation. Another 13 embryos also emerged without the mutation, but not in every cell.

The researchers tried to eliminate the problem by acting at an earlier stage, injecting the egg with the sperm and CRISPR-Cas9 simultaneously, instead of waiting to inject CRISPR-Cas9 into the already fertilized egg.

That resulted in 42 of 58 embryos, 72 percent, with two mutation-free copies of the gene in every cell. They also found no unwanted mutations in the embryos, which were destroyed after about three days.

The method was not perfect. The remaining 16 embryos had unwanted additions or deletions of DNA. Dr. Mitalipov said he believed fine-tuning the process would make at least 90 percent of embryos mutation-free.

And for disease-causing mutations on maternal genes, the same process should occur, with the fathers healthy genetic sequence being copied, he said.

But the technique will not work if both parents have two defective copies. Then, scientists would have to determine how to coax one gene to copy a synthetic DNA sequence, Dr. Mitalipov said.

Otherwise, he said, it should work with many diseases, a variety of different heritable mutations.

R. Alta Charo, a bioethicist at University of Wisconsin at Madison, who led the committee with Dr. Hynes, said the new discovery could also yield more information about causes of infertility and miscarriages.

She doubts a flood of couples will have edited children.

Nobodys going to do this for trivial reasons, Dr. Charo said. Sex is cheaper and its more fun than IVF, so unless youve got a real need, youre not going to use it.

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In Breakthrough, Scientists Edit a Dangerous Mutation From Genes in Human Embryos - New York Times

Agilis Biotherapeutics has formed a joint venture with Japans Gene Therapy Research Institution (GTRI). The alliance gives Agilis a base in Japan and a partnership with a fellow CNS specialist to support its development of adeno-associated virus (AAV) vectors and gene therapies.

Cambridge, Massachusetts-based Agilis set up the joint venture using a grant from the Japanese government. The agreement will establish an AAV manufacturing facility in Japan, from where Agilis and GTRI will work on vectors using Sf9 baculovirus and HEK293 mammalian cell systems. Agilis and GTRI plan to develop and manufacture AAV gene therapy vectors through the joint venture.

Agilis and GTRI also plan is to collaborate on the development and commercialization of certain CNS gene therapies.

GTRIs background suggests it is well-equipped to contribute to the project. The Japanese company grew out of the work of Shin-ichi Muramatsu, M.D., a scientist who sequenced AAV3 in the 1990s before going on to create AAVs designed to cross the blood-brain barrier. GTRI is working on gene therapies against diseases including Alzheimers, amyotrophic lateral sclerosis and Parkinsons that build on this research into AAVs.

Both biotechs are developing gene therapies to treat aromatic l-amino acid decarboxylase (AADC) deficiency. GTRI aims to get its candidate into the clinic in 2019. Agilispicked up its candidate from a university in Taiwan, which enrolled 18 patients in two clinical trials of the gene therapy. Those trials have taken the candidate toward a pivotal trial.

These programs may benefit from the joint venture. Working out of the Life Science Innovation Center of Kawasaki City, the joint venture intends to develop and produce AAVs for use in gene therapies against AADC deficiency and Parkinson's.

The joint venture marks the second time Agilis has looked outside of its walls for help with AAV vectors. Late in 2013, Agilis struck a deal with Intrexon that gave it access to the latters vector platform. Agilis is using the vectors to develop a treatment for Friedreichs ataxia.

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Agilis forms joint venture to advance gene therapy vectors - FierceBiotech

Impropriety among big-pharmaceutical corporations has ranged from multi-billion dollar bribery rackets, to marketing drugs to patients for uses they were never approved for by regulators, to covering up known dangerous side-effects of medications they produce and sell.

More recently, big-pharma has been embroiled in a series of price-gouging controversies over equipment and treatments. This includes the hijacking of and profiteering from a revolutionary new treatment called gene therapy.

Gene therapy, the process of re-engineering human cells to either include missing DNA to cure genetic conditions or to arm the immune system to seek and destroy disease, has been the latest hopeful technology scooped up and plundered by big-pharma.

Gene therapy promises a single shot cure to many of the diseases that have confounded humanity the most everything from diabetes to cancer, to blindness, deafness, and even various effects of aging.

At least two treatments using gene therapy have been approved for European markets.

A third that has proven in clinical trials to provide permanent remission for leukemia patients who were unresponsive to chemotherapy, appears to be close to FDA approval.

The Literal Cure for Cancer, Dangled Over the Dying

While the treatment even under experimental conditions costs approximately $20,000 to produce, pharmaceutical giant Novartis has swooped in and industry experts anticipate a markup leaving the price tag between $300,000-600,000.

The New York Times in a 2012 article titled, In Girls Last Hope, Altered Immune Cells Beat Leukemia, reported that (emphasis added):

Dr. June said that producing engineered T-cells costs about $20,000 per patient far less than the cost of a bone-marrow transplant.Scaling up the procedure should make it even less expensive, he said, but he added, Our costs do not include any profit margin, facility depreciation costs or other clinical care costs, and other research costs.

More recently, in a July 2017 Washington Post article titled, First gene therapy a true living drug on the cusp of FDA approval, its reported that:

Novartis has not disclosed the price for its therapy, but analysts are predicting $300,000 to $600,000 for a one-time infusion. Brad Loncar, whose investment fund focuses on companies that develop immunotherapy treatments, hopes the cost does not prompt a backlash. CAR-T is not the EpiPen, he said. This is truly pushing the envelope and at the cutting edge of science.

But it isnt Novartis thats pushing the envelop, or at the cutting edge of science. Charity-funded university researchers are.

Stealing From Charity

The New York Times and the Washington Post both appear to give Novartis credit for this breakthrough in their article, with NYT claiming that the company invested some $20 million on a research center to bring the treatment to market. However, that appears not to be entirely true.

It was, in fact, the Leukemia & Lymphoma Society (LLS) that funded the initial work toward this breakthrough, beginning in the late 1990s and committing some $21 million to the effort.

Novartis is indeed a partnerof LLS, but according to LLS own annual reports (2016, PDF), it is listed under the second tier of donors providing between $500,000-900,000 out of the total $35.6 million LLS received in direct gifts that year. In some years Novartis has donated even less.

LLS itself,in a 2014 press release, stated:

LLS has invested in the work of June and colleagues since 1998 and has committed to investing a total of $21 million through 2017 to get this first treatment to more patients. LLS first funded Grupp in 1992 through its career development program. LLS has also been funding another member of the team, David Porter, M.D. of University of Pennsylvania since 1994.

Elsewhere, LLS reports cite that this breakthrough in curing leukemia has attracted Novartis as a partner, never mentioning that Novartis is actually a long-term LLS partner.

In reality, it appears pharmaceutical corporations like Novartis are using charities like LLS to fund research and development that corporations themselves should be investing in. Instead, Novartis and others are poaching public and charity-funded research and breakthroughs, profiting from what is often decades of dedicated and difficult work.

Beyond LLS partners, it receives millions of dollars annually from other donors ranging from businesses unrelated to the pharmaceutical industry, to fundraising events held nationwide, to families and individuals who have experienced cancer either themselves or through a family member or friend.

The research and breakthroughs LLS funds belong to all of its donors. How the work it funded has ended up in the hands of a single corporation, facing a mark up of anywhere between 15-30 times its cost during experimental trials demands scrutiny and a detailed explanation.

Why Big-Pharma is Gouging Gene Therapy

Gene therapy overall threatens the fundamental business model pharmaceutical giants are built on that is to perpetually peddle medication that covers up the symptoms of disease rather than outright curing it.

It is a business practice that provides profits easily predicted quarter to quarter, with some medications leading to complications big-pharma also has a pill for. Something that treats a patient permanently with a single, inexpensive shot constitutes big-pharmas worst nightmare.

MIT Technology Review in an article titled, A First-of-a-Kind Gene Therapy Cure Has Struggled to Find a Market, tells the tale of another pharmaceutical corporation GlaxoSmithKline (GSK), of another revolutionary gene therapy it scooped up from research done by others, its $665,000 price tag, and why GSK along with the rest of big-pharma are disinterested in gene therapy.

The article notes:

[Alex] Pasteur [investor with F-Prime Capital Partners and interim CEO of Orchard Therapeutics] also says revenues for a rare-disease gene therapy might only ever add up to $100 million a year. Because GSK brings in $36 billion a year, Pasteur is not surprised the company is looking elsewhere for revenue. These are pimples on the back of a whale, he says. But the assets could be very interesting for someone else.

Indeed, a single shot that costs only a few thousand dollars and permanently cures people of virtually every human health infliction not only isnt profitable, but will likely put these enormous, abusive monopolies out of business for good.

Obamacare vs Turmpcare: Nobody Cares, But Innovation Cures

Education is the first step in combating the hijacking and burying of gene therapy and other innovations.

At a time when people arguing over Obamacare versus Trumpcare are realizing thatno oneactually cares about their health more than they themselves, innovation like gene therapy offers to make healthcare so affordable and effective, insurance schemes and government subsidies would be unnecessary.

But gene therapy will only gain traction if the wider public knows about it, including its implications for not only improving their own health, but improving the healthcare systems of their respective nations.

The public must also understand the true costs behind gene therapy and where money for research has come from often from public funding or charity. This knowledge allows the public to call out pharmaceutical corporations attempting to seize credit and profits entirely for themselves.

While pharmaceutical corporations invest inordinate amounts of money attempting to convince the world that they are indispensable, university researchers funded by public money and charity prove they are more often than not setting breakthroughs back, not moving them forward.

If the good people involved in LLS are capable of raising the money to fund these breakthroughs, they are capable of creating a pharmaceutical trust that can bring these cures to market with greater transparency and oversight.

Healthcare debates focused purely on political solutions and debates are frustrating. Getting behind gene therapy and other tangible healthcare innovations is something people can better invest their time, money, energy, and attention into instead.

All images in this article are from the author.

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No Matter How Bad You Thought Big-Pharma Was, This Is Worse - Center for Research on Globalization

There is new hope for muscular dystrophy patients as researchers, using gene therapy, successfully reversed the disease in dogs.

Gene therapy aims to replace missing or defective genes in the DNA of a given cell.

The technique has evolved over the years to become a viable therapy thats safe and effective, opening new paths in the management of many difficult diseases.

Not only can gene editing be used to treat pathologies, but it can also to prevent them. Only, were not there just yet.

Muscular dystrophy is the term used for a group of diseases in which musculature weakens and progressively degenerates until the patient loses most, ifnot all of their mobility.

Symptoms of muscular dystrophy often include general muscle weakness and degeneration, stiff joints, coordination and mobility troubles, and frequent falls.

In most cases a congenital condition, muscular dystrophy disorders are rare. Each disorder of muscular dystrophy is associated with distinct genetic mutations. The nature and location of the genetic mutation define the form of muscular dystrophy.

Although they can occur at any age, the onset of most MD disorders starts during childhood, and usually, affected persons dont live past 30 years of age, especially with particularly aggressive forms of the disease like Duchenne muscular dystrophy.

The most common and most studied form of muscular dystrophy is Duchenne muscular dystrophy (DMD), which affects 1 in 5,000 children at birth, and especially boys (1/3500).

Theres hope for children and other DMD patients, as a scientific experiment suggests that the disease could be reversed and a cure might be on the way.

An international research team, comprised of scientists from Genethon and Insermin France and the Royal Hollowayat the University of London UK, announced theyd managed to treat Duchenne muscular dystrophy (DMD) with gene therapy in dogs.

Their findings were published in the journal Nature Communications.

The team has shown the efficacy of gene therapy in restoring normal muscle function in 12 dogs (Golden Retrievers) affected by canine DMD, with a stabilization of clinical symptoms.

A video of these dogs before and after treatment can be found here.

Researchers injected highly functional micro-dystrophin genes (a short version of the dystrophin gene) through a drug vector (harmless virus) so that the repaired gene could produce the protein involved in muscle function.

2 years after the injection of the drug, researchers observed that all dogs demonstrated signs of significant restoration of their muscles and regained their motor skills. Not to mention that the same dogs werent expected to live past the age of 6 months.

Now, with the method has been shown to be safe and efficient in animals, the next logical step would human trials.

For the many people affected by this debilitating disease, this is a miraculous development.

The rest is here:
Gene Therapy Could Cure Muscular Dystrophy for Dogs and Humans - Edgy Labs (blog)

A safe and effective gene therapy treating Duchenne muscular dystrophy (DMD) in dogs has been demonstratedby researchers from France and the UK.

The gene therapy significantly increased the muscle strength of dogs naturally affected by DMD, improving their ability to walk, run and jump.

'This is very encouraging, as current treatments for muscular dystrophy are merely palliative and patients are under constant medical care throughout their life,' saidDr John Counsell, who was not involved in the study but works at the Gene Transfer Technology Group at University College London.

DMD is a rare, progressive disease affecting all muscles of the body, including the heart and diaphragm. It is caused bymutationsin the dystrophingene, which leads to a deficiency of dystrophinprotein. Dystrophin is important in supporting the muscle fibres during contraction; without it, the muscle fibres become damaged and eventually die.

As it is one of the largest human genes, it is technically challenging to insert the entire dystrophin gene into a viral vector, as is usually done for gene therapy. For this reason, the researchers in this study developed a gene therapy that delivers a smaller but functional version of the dystrophin gene (called micro-dystrophin). This was packaged into a non-pathogenic virus called an adeno-associated virus (AAV).

Twelve dogs with DMD received a single dose of the micro-dystrophin gene therapy and were monitored for up to two years. The researchers observed an increased amount of dystrophin protein in the dogs'muscles and a stabilisation of clinical symptoms in most of the dogs. There were no serious immune reactions to the gene therapy.

'The studies in dogs have been spectacular and exceeded our expectations,' said Professor George Dickson, who led the research at Royal Holloway University of London. My team has worked for many years to optimise a gene therapy medicine for DMD, and now the quite outstanding work of colleagues in France, in Genethon, in Nantes and in Paris has taken us close to clinical trials in DMD patients.'

In a separate study, a group of researchers from the US developed a micro-dystrophin gene therapy using a different type of AAV vector. They tested this in a recently established, severe DMD mouse model that is thought to be more like the human condition than the commonly used mdx mouse.

15 weeks after AAV injection, the researchers detected an increased amount of dystrophin protein in the mouse muscles. There were also improvements in muscle function and a reduction in muscle scarring and inflammation.

Whilst evaluating cardiac function, the researchers unexpectedly found pathological changes in the hearts of control mice, which meant that they were similar to the DMD hearts. For this reason, they could not evaluate the effect of the micro-dystrophin gene therapy on cardiac function and concluded that the mouse was not a good model for DMD-associated cardiomyopathy.

Read this article:
BioNews - Gene therapy reverses muscular dystrophy in dogs in ... - BioNews

Xconomy Boston

One day after the release of a Nature Medicine paper warning of the potential hazards of testing CRISPR-Cas9 gene editing in humans, Homology Medicines, a startup advancing a different genetic surgery technique, has just grabbed a big round of funding to make its own clinical push.

Homology, of Bedford, MA, wrapped up an $83.5 million Series B round this morning. A wide group of investors led by Deerfield Management provided the funding, bringing the companys total amount raised to a whopping $127 million since it was formed last year.

Homology is making the bold claim that its underlying science, technology it calls AMEnDR, is a better version of existing gene editing methods, among them the CRISPR-Cas9 technology that has taken the scientific research world by storm and has led to the formation of three now publicly traded companies, Editas Medicine (NASDAQ: EDIT), Intellia Therapeutics (NASDAQ: NTLA), and CRISPR Therapeutics (NASDAQ: CRSP).

CRISPR gene editing is a two-part biological system that researchers can use to help irreversibly alter DNA. The three companies are involved in a high-stakes race to use the technology to develop human therapeutics, with the first clinical trials expected to begin next year. Yet one of the fears involved in bringing the technology to human trials is the possibility of off-target effectsa genetic surgery error that causes irreparable damage, like cancer. One of the fields pioneers, Feng Zhang of the Broad Institute of MIT and Harvard, just co-authored a paper in Nature Medicine urging caution about the rush to move forward. Zhang and colleague David Scott argued that researchers should analyze patients DNA before giving them CRISPR-based drugs, citing the myriad differences between each persons genetic makeup.

Homology isnt using CRISPR, like its publicly traded rivals. Instead, its recreating a natural biological process known as homologous recombination, which cells in humans and other species do to repair DNA damage or, in the case of bacteria, to improve their genetic diversity. In homologous recombination, one chromosome essentially swaps one short DNA sequence for another similar one. Homology aims to engineer a piece of healthy DNA, pack it into a type of adeno-associated virus, or AAVa delivery tool commonly used in gene therapy and gene editing technologiesand infuse it into the body. The virus carrying the DNA locks on to the cell that needs a genetic fix, enters it, and releases its DNA payload. The healthy DNA then swaps places with the faulty gene inside the patients cells. If and when the cells divide, the new cells would carry the fixed gene, not the faulty one. One potential benefit of this approach is there may be less likelihood of an off-target error, like mutations in the target DNA that cause cancer, than with CRISPR.

Thats the hope, but the technology hasnt been tested in humans as of yet. With the new cash, however, Homology is getting a shot to try. In a statement, Homology CEO Arthur Tzianabos said the funding will help Homology bring its first drug candidate toward the clinic, though he didnt specify how long that might take. The company is focusing on rare diseasesno surprise given Tzianabos, chief operating officer Sam Rasty, and chief scientific officer Albert Seymour all worked with one another at rare disease giant Shire (NASDAQ: SHPG). According to its website, the company will develop therapies for inborn errors of metabolism, and Duchenne muscular dystrophy and cystic fibrosis are among its potential targets as well. (Duchenne and cystic fibrosis are early targets of CRISPR-based medicines as well.)

Fidelity Management and Research, Novartis, Rock Springs Capital, HBM Healthcare Investments, Arch Venture Partners, Temasek, 5AM Ventures, Maverick Ventures, Vida Ventures, Vivo Capital, and Alexandria Venture Investments also took part in the funding. Heres more on Homology, and gene editing with CRISPR-Cas9.

Ben Fidler is Xconomy's Deputy Biotechnology Editor. You can e-mail him at bfidler@xconomy.com

View original post here:
Homology Med Bags $83.5M More, Fueling Push For Gene Editing Twist - Xconomy

BALTIMORE Although there are medications to treat depression, many scientists arent sure why theyre effective and why they dont work for everyone.

Researchers at the University of Maryland School of Medicine believe they may have found a key to the puzzle of major depression that could lead to therapies for those who dont respond to medications already on the market.

A study by the researchers has identified the central role a gene known as Slc6a15 plays in either protecting from stress or contributing to depression, depending on its level of activity in a part of the brain associated with motivation, pleasure and reward seeking.

Published in the Journal of Neuroscience in July, the study is the first to illuminate in detail how the gene works in a kind of neuron that plays a key role in depression, the according to the medical school.

Specifically, the researchers found that mice with depression had reduced levels of the genes activity, while those with high levels of the genes activity handled chronic stress better.

Though senior researcher Mary Kay Lobos primary studies were done with mice, she also examined the brains of people who had committed suicide and found reduced levels of the genes activity, confirming a likely link.

She hopes now that drugs could be developed that would encourage the genes activity.

I thought it was fascinating we had this system in place that allows us to go after things or be motivated or have pleasure and I was interested in how it becomes dysfunctional in certain diseases like depression, Lobo said. I hope that we can identify molecules that could potentially be therapeutically treated or targeted to treat depression.

Lobo and her colleagues have been examining the gene for years. In 2006, they discovered that it was more common among specific neurons in the brain that they later learned were related to depression. Five years later, other researchers learned that the gene played a role in depression and Lobo and her research colleagues decided to investigate what that role is in those specific neurons.

About 15 million adults, or 6.7 percent of all U.S. adults, experience major depression in a given year, according to the Anxiety and Depression Association of America. It is the leading cause of disability for Americans ages 15 to 44. It is more prevalent in women and can develop at any age, but the median age of onset is 32.5.

David Dietz, an associate professor in the Department of Pharmacology and Toxicology at the State University of New York at Buffalo, said little was known previously about the biological basis of depression in the brain. Many drugs used to treat depression were discovered serendipitously, he said, and it wasnt clear why they worked.

Were starting to really get an idea of what does the depressed brain look like, Dietz said. When you put the whole puzzle together, you see where the problem is. For too long weve been throwing things at individual pieces. Its so complex and we have so little information that it was almost bound to be that way. For the first time this is one of those bigger pieces you can slide into the jigsaw puzzle.

Lobo said its not clear yet how Slc6a15 works in the brain, but she believes it may be transporting three types of amino acids into a subset of neurons called D2 neurons in a part of the brain called the nucleus accumbens. The nucleus accumbens and D2 neurons are known to play a role in pleasure, activating when one eats a delicious meal, has sex or drinks alcohol.

The amino acids would then be synthesized into neurotransmitters. Depression previously has been linked to imbalances of the neurotransmitters serotonin, norepinephrine and dopamine.

So even though people may have proper levels of amino acids in their bodies, the neurons in their brains that need them may not be getting enough if the transporter is not working as it should.

This gene is critical for putting very specific amino acids in the right place so that neurotransmitters can be synthesized, said A.J. Robison, an assistant professor in the Department of Physiology at Michigan State University. Its the location, location, location idea. Its not the amino acids, its where theyre at and in which cells.

Robison said Lobos next step would be discovering more about how the transporter gene works.

The fact that this transporter seems to be important is what the paper shows and how it does it is not shown, and thats a challenge for her, he said. Figuring out the how of it is the next step and Dr. Lobo is particularly positioned to do it.

Lobos team was able to use gene therapy, a form of therapy in the early stages of being studied in humans, in the mice to boost the genes activity. The mice were exposed to larger, more aggressive mice, which usually causes depressive symptoms. But the gene therapy helped protect the mice against the stress, the team found. When the team reduced the genes activity in the mice, just one day of exposure to the aggressive mice was enough to cause symptoms of depression.

Gene therapy is starting to be used in the treatment of some types of cancers, but Lobo said science had not yet advanced to the point where it can be used for treating neurological issues in human patients. A more likely treatment would be a drug that targets the genes activity directly, she said.

I think this is a major step toward our understanding of the precise maladaptive changes that occur in response to stress, said Vanna Zachariou, an associate professor in the Department of Neuroscience at the Icahn School of Medicine at Mount Sinai. It can be a more efficient way to target depression because its not simply targeting monoamine receptors or dopamine but targeting molecular adaptations that occur. It doesnt act necessarily as the drugs we have available, so it might create an alternative avenue to treat depression.

Lobo said she wouldnt refer to Slc6a15 as a depression gene, saying the disease was complex and could have many factors.

I wouldnt say theres one depression gene she said. A number of things play a role, and also theres no depression neuron, theres multiple depression neurons.

There also may be different types of depression with different symptoms, she said. With the disease, some sufferers sleep a lot, while others sleep a lot less, for example.

With all these complex diseases, its hard to link it to something, she said. Like Huntingtons disease, we know theres a specific gene that causes Huntingtons disease. For depression we dont have that.

See more here:
Maryland scientists research gene linked to depression | The ... - The Spokesman-Review

Global Cancer Gene Therapy Market Research Report 2017 to 2022presents an in-depth assessment of the Cancer Gene Therapy including enabling technologies, key trends, market drivers, challenges, standardization, regulatory landscape, deployment models, operator case studies, opportunities, future roadmap, value chain, ecosystem player profiles and strategies. The report also presents forecasts for Cancer Gene Therapy investments from 2017 till 2022.

This study answers several questions for stakeholders, primarily which market segments they should focus upon during the next five years to prioritize their efforts and investments. The Cancer Gene Therapy markets are highly fragmented due to the presence of numerous small and large vendors. Most of the international pharmaceutical companies are facing challenges such as price pressure, regulatory constraints, and competition from local and other international pharmaceutical companies in the Cancer Gene Therapy markets. The competitive environment in the market is expected to intensify with an increase in product extensions, technological innovations, and increase in mergers and acquisitions.

These stakeholders include Cancer Gene Therapy manufacturers such as : Cell Genesys, Advantagene, GenVec, BioCancell, Celgene and Epeius Biotechnologies, Introgen Therapeutics, ZIOPHARM Oncology, MultiVir, Shenzhen SiBiono GeneTech.

Inquire for sample of report @:

https://www.marketinsightsreports.com/reports/07318362/global-cancer-gene-therapy-market-professional-survey-report-2017/inquiry

Primary sources are mainly industry experts from core and related industries, and suppliers, manufacturers, distributors, service providers, and organizations related to all segments of the industrys supply chain. The bottom-up approach was used to estimate the global market size of Cancer Gene Therapy based on end-use industry and region, in terms of value. With the data triangulation procedure and validation of data through primary interviews, the exact values of the overall parent market, and individual market sizes were determined and confirmed in this study.

Secondly the study, besides estimating the Cancer Gene Therapy market potential till 2022, analyzes on who can be the market leaders and what partnerships would help them to capture the market share. The report gives an overview about the dynamics of the market, by discussing various aspects such as drivers, restraints, Porters 5 forces, value chain, customer acceptance and investment scenario.

TheGlobal Cancer Gene Therapy marketconsists of different international, regional, and local vendors. The market competition is foreseen to grow higher with the rise in technological innovation and M&A activities in the future. Moreover, many local and regional vendors are offering specific application products for varied end-users. The new vendor entrants in the market are finding it hard to compete with the international vendors based on quality, reliability, and innovations in technology.

The research report presents a comprehensive assessment of the market and contains thoughtful insights, facts, historical data, and statistically supported and industry-validated market data. It also contains projections using a suitable set of assumptions and methodologies. The research report provides analysis and information according to categories such as market segments, geographies, types, technology and applications.

Global Cancer Gene Therapy Sales (K Units) and Revenue (Million USD) Market Split by Product Type:

Global Cancer Gene Therapy Sales (K Units) by Application (2016-2022)

by Application

(2016-2022)

The research provides answers to the following key questions:

This independent 109 page report guarantees you will remain better informed than your competition. With over 150 tables and figures examining the Cancer Gene Therapy market, the report gives you a visual, one-stop breakdown of the leading products, submarkets and market leaders market revenue forecasts as well as analysis to 2022.

Browse Full Report @:

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Geographically, this report is segmented into several key Regions, with production, consumption, revenue (million USD), and market share and growth rate of Storage Area Network Switch in these regions, from 2012 to 2022 (forecast), covering

by Regions

The report provides a basic overview of the Cancer Gene Therapy industry including definitions, classifications, applications and industry chain structure. And development policies and plans are discussed as well as manufacturing processes and cost structures.

Then, the report focuses on global major leading industry players with information such as company profiles, product picture and specifications, sales, market share and contact information. Whats more, the Cancer Gene Therapy industry development trends and marketing channels are analyzed.

The report segments this market based on products, portability, methods, applications, and end users. Among various end users, the hospitals segment is expected to account for the largest share of the market and is expected to grow at the highest CAGR from 2014 to 2019. The high growth in this segment can be attributed to the rising rate of maternal mortality and fetal birth defects, and increasing number of initiatives taken by government organizations for improving prenatal care.

The research includes historic data from 2012 to 2016 and forecasts until 2022 which makes the reports an invaluable resource for industry executives, marketing, sales and product managers, consultants, analysts, and other people looking for key industry data in readily accessible documents with clearly presented tables and graphs. The report will make detailed analysis mainly on above questions and in-depth research on the development environment, market size, development trend, operation situation and future development trend of Cancer Gene Therapy on the basis of stating current situation of the industry in 2017 so as to make comprehensive organization and judgment on the competition situation and development trend of Cancer Gene Therapy Market and assist manufacturers and investment organization to better grasp the development course of Cancer Gene Therapy Market.

The study was conducted using an objective combination of primary and secondary information including inputs from key participants in the industry. The report contains a comprehensive market and vendor landscape in addition to a SWOT analysis of the key vendors.

The report is a compilation of first-hand information, qualitative and quantitative assessment by industry analysts, inputs from industry experts and industry participants across the value chain. The report provides in-depth analysis of parent market trends, macro-economic indicators and governing factors along with market attractiveness as per segments. The report also maps the qualitative impact of various market factors on market segments and geographies.

There are 15 Chapters to deeply display the global Cancer Gene Therapy market.

Chapter 1, to describe Cancer Gene Therapy Introduction, product scope, market overview, market opportunities, market risk, market driving force;

Chapter 2, to analyze the top manufacturers of Grain and Seed Cleaning Equipment, with sales, revenue, and price of Grain and Seed Cleaning Equipment, in 2016 and 2017;

Chapter 3, to display the competitive situation among the top manufacturers, with sales, revenue and market share in 2016 and 2017;

Chapter 4, to show the global market by regions, with sales, revenue and market share of Grain and Seed Cleaning Equipment, for each region, from 2012 to 2017;

Chapter 5, 6, 7,8and 9, to analyze the key regions, with sales, revenue and market share by key countries in these regions;

Chapter 10and 11, to show the market by type and application, with sales market share and growth rate by type, application, from 2012 to 2017;

Chapter 12, Cancer Gene Therapy market forecast, by regions, type and application, with sales and revenue, from 2017 to 2022;

Chapter 13, 14 and 15, to describe Cancer Gene Therapy sales channel, distributors, traders, dealers, Research Findings and Conclusion, appendix and data source.

Link:
Cancer Gene Therapy Market Analysis And Review By Experts 2017 - Equity Insider (press release)

Although medications exist to treat depression, many scientists arent sure why theyre effective and why they dont work for everyone.

Researchers at the University of Maryland School of Medicine believe they may have found a key to the puzzle of major depression that could lead to therapies for those who dont respond to medications already on the market.

A new study by the researchers has identified the central role a gene known as Slc6a15 plays in either protecting from stress or contributing to depression, depending on its level of activity in a part of the brain associated with motivation, pleasure and reward seeking.

Published in the Journal of Neuroscience in July, the study is the first to illuminate in detail how the gene works in a kind of neuron that plays a key role in depression, according to the University of Maryland School of Medicine.

Specifically, the researchers found that mice with depression had reduced levels of the genes activity, while those with high levels of the genes activity handled chronic stress better.

Though senior researcher Mary Kay Lobos primary studies were done with mice, she also examined the brains of people who had committed suicide and found reduced levels of the genes activity, confirming a likely link.

She hopes now that drugs could be developed that would encourage the genes activity.

I thought it was fascinating we had this system in place that allows us to go after things or be motivated or have pleasure and I was interested in how it becomes dysfunctional in certain diseases like depression, Lobo said. I hope that we can identify molecules that could potentially be therapeutically treated or targeted to treat depression.

Lobo and her colleagues have been examining the gene for years. In 2006, they discovered that it was more common among specific neurons in the brain that they later learned were related to depression. Five years later, other researchers learned the gene played a role in depression and Lobo and her research colleagues decided to investigate what that role is in those specific neurons.

About 15 million adults, or 6.7 percent of all U.S. adults, experience major depression in a given year, according to the Anxiety and Depression Association of America. It is the leading cause of disability for Americans aged 15 to 44. It is more prevalent in women and can develop at any age, but the median age of onset is 32.5.

David Dietz, an associate professor in the Department of Pharmacology and Toxicology at the State University of New York at Buffalo, said little was known previously about the biological basis of depression in the brain. Many drugs used to treat depression were discovered serendipitously, he said, and it wasnt clear why they worked.

Were starting to really get an idea of what does the depressed brain look like, Dietz said. When you put the whole puzzle together, you see where the problem is. For too long weve been throwing things at individual pieces. Its so complex and we have so little information that it was almost bound to be that way. For the first time this is one of those bigger pieces you can slide into the jigsaw puzzle.

Lobo said its not clear yet how Slc6a15 works in the brain, but she believes it may be transporting three types of amino acids into a subset of neurons called D2 neurons in a part of the brain called the nucleus accumbens. The nucleus accumbens and D2 neurons are known to play a role in pleasure, activating when one eats a delicious meal, has sex or drinks alcohol.

The amino acids would then be synthesized into neurotransmitters. Depression previously has been linked to imbalances of the neurotransmitters serotonin, norepinephrine and dopamine.

So even though people may have proper levels of amino acids in their bodies, the neurons in their brains that need them may not be getting enough if the transporter is not working as it should.

This gene is critical for putting very specific amino acids in the right place so that neurotransmitters can be synthesized, said A.J. Robison, an assistant professor in the Department of Physiology at Michigan State University. Its the location, location, location idea. Its not the amino acids, its where theyre at and in which cells.

Robison said Lobos next step would be discovering more about how the transporter gene works.

The fact that this transporter seems to be important is what the paper shows and how it does it is not shown, and thats a challenge for her, he said. Figuring out the how of it is the next step and Dr. Lobo is particularly positioned to do it.

Lobos team was able to use gene therapy, a form of therapy in the early stages of being studied in humans, in the mice to boost the genes activity. The mice were exposed to larger, more aggressive mice, which usually causes depressive symptoms. But the gene therapy helped protect the mice against the stress, the team found. When the team reduced the genes activity in the mice, just one day of exposure to the aggressive mice was enough to cause symptoms of depression.

Gene therapy is starting to be used in the treatment of some types of cancers, but Lobo said science had not yet advanced to the point where it can be used for treating neurological issues in human patients. A more likely treatment would be a drug that targets the genes activity directly, she said.

I think this is a major step toward our understanding of the precise maladaptive changes that occur in response to stress, said Vanna Zachariou, an associate professor in the Department of Neuroscience at the Icahn School of Medicine at Mount Sinai. It can be a more efficient way to target depression because its not simply targeting monoamine receptors or dopamine but targeting molecular adaptations that occur. It doesnt act necessarily as the drugs we have available, so it might create an alternative avenue to treat depression.

Lobo said she wouldnt refer to Slc6a15 as a depression gene, saying the disease was complex and could have many factors.

I wouldnt say theres one depression gene she said. A number of things play a role, and also theres no depression neuron, theres multiple depression neurons.

There also may be different types of depression with different symptoms, she said. With the disease, some sufferers sleep a lot, while others sleep a lot less, for example.

With all these complex diseases, its hard to link it to something, she said. Like Huntingtons disease, we know theres a specific gene that causes Huntingtons disease. For depression we dont have that.

cwells@baltsun.com

See the rest here:
University of Maryland scientists research gene linked to depression - Baltimore Sun

The idea of treating Duchenne muscular dystrophy by replacing defective dystrophin genes with normal ones is not new, but previous approaches have been limited by the gene's size. A University of Missouri-led team has developed a new gene transfer method to solve this problem.

Duchenne is caused by mutations in the dystrophin gene, which codes for a protein of the same name. Without the stabilizing dystrophin protein, muscle fibers, including those in the heart, eventually weaken and die.

Gene therapy seeks to treat DMD by restoring dystrophin production. Adeno-associated viruses (AAV) are usedto deliver the gene, as they do not cause disease in humans. But because the dystrophin gene is too large for the virus to carry, researchers had to developmodified versions of the gene, dubbed mini- or microdystrophin, for gene therapy.

Problem is, editing the gene can leave out a binding site for the enzyme nNos, which is important for blood flow during muscle contraction, the researchers said. So the team, which also includes scientists from the University of Washington, developed a new AAV microdystrophin vector that has an nNos binding site and a component that promotes dystrophin expression in muscle cells.

RELATED: Shortened telomeres linked to heart damage in Duchenne muscular dystrophy

They injected the vector into mouse models that resemble DMD.Fifteen weeks later, they foundall 10 of the treated mice had high levels of the microdystrophin protein in all of their skeletal muscles. The treatment reduced inflammation, scarring and hardening in the mices muscles and restored their muscle strength.

The research, published in Molecular TherapyMethods & Clinical Development, is encouraging, but a new treatment is a few years off.

"There is still a lot to learn about the dystrophin gene, the dystrophin protein, Duchenne muscular dystrophy disease mechanisms, and gene transfer vectors," said senior author Dongsheng Duan, of the University of Missouri, in a press release. "Future studies will hopefully allow us to develop a more effective therapy to treat Duchenne muscular dystrophy in the coming years."

Most of the recent attention in DMD has gone to Sarepta, which gotits controversial Duchenne drug past the FDAafter much debate. Now the company is chasing other treatments for the disease. In January, Sarepta penned a microdystrophin research deal with Nationwide Childrens Hospital and in June, it inked a deal that gave it the option to co-develop France-based Genethons microdystrophin program.

Sareptas drug, Exondys 51, only works in patients with a particular mutation, about 13% of the total DMD patient population. Its new research partnerships could yield gene therapies that would treat many morepatients.

Continued here:
U. of Missouri-led scientists improve gene transfer in Duchenne therapy - FierceBiotech

LONDON (Reuters) - GlaxoSmithKline is swimming against the tide by getting out of treatments for rare diseases at a time when rivals like Sanofi and Shire see the field as a rich seam for profits.

Successful medicines for rare conditions are potentially very lucrative, since prices frequently run into hundreds of thousands of dollars, but patient numbers can be extremely low.

New GSK Chief Executive Emma Walmsley announced the strategic review and potential divestment of rare diseases on Wednesday as part of a wide-ranging drive to streamline pharmaceutical operations.

It follows a less than impressive experience for GSK in the field, including the fact that its pioneering gene therapy Strimvelis only secured its first commercial patient in March, 10 months after it was approved for sale in Europe in May 2016.

Since then a second patient has also been treated and two more are lined up to receive the therapy commercially, a spokesman said.

Strimvelis, which GSK developed with Italian scientists, is designed for a tiny number of children with ADA Severe Combined Immune Deficiency (ADA-SCID). SCID is sometimes known as "bubble baby" disease, since those born with it have immune systems so weak they must live in germ-free environments.

The new treatment became the first life-saving gene therapy for children when it was approved last year, marking a step forward for the emerging technology to fix faulty genes.

Walmsley said GSK was not giving up on gene and cell therapy entirely. Research will be focused in future in areas with larger potential patient numbers, including oncology.

Reporting by Ben Hirschler; Editing by Adrian Croft

Original post:
GSK gives up on rare diseases as gene therapy gets two customers - Reuters

An FDA advisory panel will make the call July 12 to recommend for or against agency approval of the first gene therapy. A favorable decision could see the regulator sanction the treatment by early this fall. Drug manufacturer Novartis and the University of Pennsylvania doctors and scientists who tested it are holding out hope for CAR T-cell therapy, which uses patients' own genetically modified immune cells to fight blood cancers. In a multinational trial of pediatric patients, it achieved remission in 83% of participants67% of whom remained in remission 1 year later. While CAR T-cell therapy initially would be offered to children and young adults not responding to standard leukemia treatment, research has shown it to be effective in adults as well. Substantial concerns about safety and cost, however, could sway the FDA committee away from approval. Analysts' projections put the price for a one-time infusion at $300,000$600,000, and there also is the risk of serious adverse effectsincluding neurotoxicity and cytokine release syndrome. Novartis is addressing the safety issue by planning a contained launch of the product, rather than simply unleashing it on the entire market. Under its plan, only 3035 medical centers would be authorized to administer CAR T-cell therapy, most having participated in the clinical trial and all having received extensive training.

Read the original post:
First gene therapy on the cusp of FDA approval - Pharmacy Today, American Pharmacists Association, pharmacist.com